Diabetes mellitus is a disease of major global importance, increasing in frequency at almost epidemic rates, such that the worldwide prevalence in 2006 is 170 million people and predicted to at least double over the next 10-15 years. Diabetes is characterized by a chronically raised blood glucose concentration (hyperglycemia), due to a relative or absolute lack of the pancreatic hormone, insulin. Within the healthy pancreas, beta cells, located in the islets of Langerhans, continuously produce and secrete insulin according to the blood glucose levels, maintaining near constant glucose levels in the body.
Much of the burden of the disease to the patient and to health care resources is due to the long-term tissue complications, which affect both small blood vessels (microangiopathy, causing eye, kidney and nerve damage) and large blood vessels (causing accelerated atherosclerosis, with increased rates of coronary heart disease, peripheral vascular disease and stroke). The Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are greatly related to the degree of altered glycemia as quantified by determinations of glycohemoglobin (HbAlc). [DCCT Trial, N Engl J Med 1993; 329: 977-986, UKPDS Trial, Lancet 1998; 352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N Engl J Med 2005; 353, (25): 2643-53]. Thus, maintaining normoglycemia by frequent glucose measurements and adjustment of insulin delivery accordingly is of utmost importance.
Insulin pumps have been available which can deliver rapidly acting insulin 24 hours a day, for example, through a cannula inserted subcutaneously. The total daily insulin dose can be divided into basal and bolus doses. Basal insulin dose or simply basal insulin can be delivered continuously over 24 hours, and keeps the blood glucose levels in an acceptable range between meals and overnight. Diurnal basal rates can be pre-programmed or manually changed according to various past or future daily activities.
Insulin bolus doses or simply boluses can be delivered to counteract carbohydrates loads before or after meals or during episodes of high blood sugar levels. The amount of insulin (bolus dose) can depend on several parameters that can be related to the intake, blood sugar, and patient's specific parameters including the following:                an amount of carbohydrates (Carbs) in a meal to be consumed, alternatively defined as “servings”, wherein 1 serving=15 grams of Carbs;        carbohydrate-to-insulin ratio (CIR), i.e. the amount of carbohydrates balanced by one unit of insulin;        insulin sensitivity (IS), i.e. the amount of blood glucose value lowered by one unit of insulin;        current blood glucose level (CBG);        target blood glucose level (TBG), i.e. the desired blood glucose level. TBG for most people suffering from diabetes is in the range of 90-130 mg/dL;        residual insulin (RI), i.e. the amount of still active insulin remaining in the body after recent bolus deliveries. This parameter can be relevant in a situation when there is a short time interval between delivery of boluses (e.g. less than 5 hours); and        parameters that influence carbs absorption and consequently rate of sugar rise in blood such as Glycemic Index (GI), fat or fibers content, etc.        
The insulin sensitivity (IS) can be determined, for example, according to the so-called “2200 to 1600 rules” commonly used by type 1 diabetes patients using rapid acting insulin (e.g. Humalog®, Novolog®). The user's IS can be determined by dividing the value corresponding to a certain rule by the total daily dose of rapid-acting insulin. For example, if the total daily insulin dose is 40 units and the “1800” rule is used, the insulin sensitivity factor would be 1800 divided by 40=45 mg/dl/unit. FIG. 1 illustrates the insulin sensitivity expressed as point drop per unit of insulin corresponding to the various rules (adapted from Using Insulin written by John Walsh© 2003).
The carb to insulin ratio (CIR) can be determined, for example, according to the so-called “450 to 500 rules” commonly used by type 1 diabetes patients using rapid acting insulin (e.g. Humalog®, NovoLog®). The user CIR can be determined by dividing the value corresponding to a certain rule by the total daily dose of rapid-acting insulin. For example, if the total daily insulin dose is 40 units and the 450 rule is used, the carb to insulin ratio (CIR) would be 450 divided by 40=11 gram. FIG. 2 provides an example amount of carbs (in grams) that can be balanced by 1 unit of insulin (CIR) according to various rules (adapted from Using Insulin© 2003).
The residual insulin can be determined according to the pharmacokinetics of rapid acting insulin (e.g. Humalog®, NovoLog®). FIG. 3 illustrates one example of amount of residual insulin (in units) after 1-5 hours from a previous given bolus (adapted from Using Insulin© 2003).
The amount of insulin in the bolus to be delivered can be established by calculations using equations that include the abovementioned parameters, as described in U.S. Pat. No. 6,936,029 assigned to Medtronic MiniMed, or they can be selected by a method for selection of the desired bolus dose, as described in co-owned, co-pending U.S. patent application Ser. No. 12/051,400 and International Patent Application No. PCT/IL2008/000380, the disclosures of which are incorporated by reference in their entireties.
The bolus delivery pattern refers to a rate or rates at which the bolus dose is administered over time. The glycemic index (GI) or fat content of the intake influence carbs absorption and consequently bolus delivery time and pattern. The GI can be expressed as a ranking system for carbohydrates contained in food according to how they affect the blood glucose levels. Glucose, the fastest-acting carbohydrate, is given a value of 100, and the other carbs are ranked relative to that value. Ripeness, cooking time, fiber, and fat content in the food can all impact GI. A low GI food will release glucose more slowly and steadily. A high GI food causes a more rapid rise in blood glucose. For example, FIG. 4 depicts different types of foods and their GI. A meal containing, for example, a carbohydrate load having high glycemic index (e.g. lemonade, white bread) would require insulin to be delivered immediately to counteract the carbohydrates rapidly absorbed through the gut. A meal containing a carbohydrate load having a low glycemic index (e.g. milk, ice cream) would require insulin to be delivered over a long period of time to counteract the slowly absorbed carbohydrates.
Currently, most insulin pumps allow the user to program the bolus delivery pattern. The most common delivery patterns are:                1. immediate (“regular”, “normal”) bolus—the entire bolus dose is delivered at the fastest pump delivery rate;        2. extended bolus—the entire bolus is delivered over a long period of time (e.g. 30 min-8 hours) at a constant rate; and        3. combined bolus (“dual wave”)—some of the bolus dose is delivered as an immediate bolus and the rest of the bolus dose is delivered as an extended bolus. Usually the ratio (in percentage) between the immediate bolus portion and the extended bolus portion can be selected by the patient, e.g. as described in U.S. Pat. No. 6,852,104 assigned to Smiths Medical MD (formerly Deltec Medical).        
In current devices, in order to adjust a bolus delivery pattern, a user can program one or more of the following parameters: duration of bolus delivery (for extended bolus and extended portion of a combined bolus), ratio between the immediate bolus portion and extended bolus portion (for combined bolus). In practice, a user's decision about the bolus pattern is arbitrary and based merely on intuition. Additional drawbacks associated with conventional pumps that include means for programming bolus pattern are:                the necessity for data input which complicates the user interface because it requires navigation through several displays which are not user-friendly; and        difficulties for young children may to master data input since it is associated with reading and typing alpha-numeric parameters.        
The following definitions are provided for terms used herein:                “GI” (Glycemic Index) refers to a ranking system for carbohydrates based on how they affect blood glucose levels.        “GL” (Glycemic Load”) refers to the amount of carbs in a meal multiplied by the GI of the meal divided by 100.        “CIR” (Carbohydrate to Insulin Ratio) refers to the amount of carbohydrates balanced by one unit of insulin.        “IS” (Insulin Sensitivity) refers to the amount of blood glucose value lowered by one unit of insulin.        “Dose” or “bolus dose” refers to amount of insulin administered to counteract carbohydrates in a meal (for example 6 units (6 U)).        “Delivery pattern” refers to the pattern of delivery over time of administered dose (for example a dose of 6 U may be delivered as follow—4 U in 2 hours and 2 U in additional 4 hours).        “Bolus” refers to the combination of bolus dose and delivery pattern.        “Grid” or “bolus grid” refers to a matrix of 2 or more dimensions constructed of cells. (for example a 3D matrix including the following axes: X—carbs, Y—blood glucose, Z—glycemic index) Each grid is dedicated to a different combination of parameters like CIR, IS, and target blood glucose (TBG).        “Cell” refers to one of many units comprising a grid. Each cell represents a combination of parameters exhibited on the different axes of the grid (e.g. combination of ranges of GI, BG, and carb load).        